This invention relates to light detectors and more particularly to high quantum efficiency point light detectors particularly adapted for detecting low levels of fluorescence.
In many analytical situations, fluorescing molecules are attached to molecules of interest to aid in their detection. Upon illumination, fluorescence indicates the presence of a tagged moiety. The level of fluorescence is often quite low resulting in a low signal-to-noise ratio.
In systems using a point detector such as a photomultiplier tube (PMT) the achieved signal-to-noise ratio is often limited by the number of photons detected, i.e., by the number of photons that result in the generation of a photoelectron in a photocathode that is subsequently detected as a multi-electron pulse at the anode within the PM. The ratio of the number of electron pulses generated to the number of incident photons is called the quantum efficiency of the detector. PMT""s have a quantum efficiency that is significantly lower than one. Although detectors that measure electric charges generated by incident radiation such as charge-coupled devices (CCD""s) are known to have a much higher quantum efficiency than PMT""s, it has been assumed that the PMT is the best solution available for use as a point detector. This was the case because CCD""s, though having higher quantum efficiency, suffer from dark current-related electron shot noise and especially from readout noise.
In multi-pixel (imaging) situations with very long integration times such as in astronomical photography the multiple readout of a CCD has been used. However, the inventors herein are unaware of any prior art realization that a CCD can be modified into a point detector that can outperform a PMT in terms of achieved signal-to-noise ratio.
The high quantum efficiency point detector system according to the invention includes a light source generating a light beam having an area, and a detector for receiving the light beam, the detector having a cell size comparable to the light beam area. The detector may be any detector that measures electric charges generated by incident radiation such as a charge-coupled device (CCD). The cell may have a single relatively large pixel or it may have an array of two or more pixels. The system further includes a readout capacitor and apparatus for transferring, multiple times, charge from the detector to the capacitor and back. It is preferred that a plurality of transfer and readout capacitors be provided for multiple readouts. Further, readout noise can be reduced by reading out a single CCD element multiple times and averaging the results.